During the past year we have evaluated the possible role of class II antigens in ocular disorders. Class II antigens, HLA-DR in man and Ia in the mouse, are membrane bound glycoproteins encoded by genes of the MHC. These cell surface proteins play a pivotal role in immune responses, are present only on selected cell types, and their expression is regulated by the lymphokine, interferon-gamma. We have identified alterations in this system in both retinal degenerative disorders and in ocular inflammatory diseases (Uveitis, Sympathetic Ophthalmia and Sjogren's Syndrome). In the retinal degenerative disorder, retinitis pigmentosa, there is an alteration in the expression and regulation of class II antigens on blood monocytes. These findings were extended to demonstrate the presence of HL-DR on a regulatory cell within the eye, the retinal pigment epithelial cell (RPE). The concept of activation of class II antigen on RPE cells is substantiated by both immunofluorescent and immunoperoxidase techniques which revealed the absence of HLA-DR on RPE cells from normal individuals and the presence of these antigens on RPE cells from patients with RP and inflammatory eye diseases. Moreover, the sequential devlopment of class II antigens in experimental autoimmune uveitis (EAU) in the rat revealed the expression of class II antigens on RPE cells prior to and during the development of the disease. In another automimmune disorder, Sjogren's Syndrome, we have identified the activation of class II antigens on salivary gland duct cells and are presently evaluating ocular tissue from these patients. These findings suggest that perturbation of ocular tissue via ocular inflammation or degeneration can lead to the modification of antigen expression on ocular cells. Furthermore the presence of HLA-DR on RPE cells may alter the pathogenicity of these ocular diseaes.